The nature of ganglioside distribution throughout the neuron requires reinvestigation in view of evidence recently uncovered in our laboratory that they are not specifically localized at the nerve-ending. Since our results indicate distribution over the entire neuronal surface (including cell body and processes as well as synaptic membrane), biochemical and immunocytochemical experiments are planned to further test this hypothesis. Axonal transport as the primary mechanism for disseminating gangliosides to processes and nerve-endings will be further examined with respect to flow patterns of individual molecular species to membranes of neuronal processes and nerve-endings. We also plan to continue our investigation of the axonal transport process as it applies to other membrane lipids. Studies will be carried out to determine the origin and properties of the small pool of soluble gangliosides, recently discovered by our group to be present as a distinct metabolic compartment at the nerve-ending (and possible elsewhere in the neuron). We shall follow up recent work by our group showing transaxonal migration of certain molecules (e.g., serine) that subsequently become incorporated into myelin lipids in young rabbits. This study will explore a possible relationship between axonal transport and neuron-glia interaction. We shall continue our work in the area of structure determination of gangliosides in normal brain and in neurological diseases; this will include a ganglioside (G2A) previously found to be especially abundant in multiple sclerosis plaques. Additional gangliosides will be isolated from peripheral nerve and their structures determined.